The general objectives of the proposed research are to study factors which influence the action of the anticoagulants such as dicumarol and warfarin. Among the factors which will be studied are: 1) the effect of other drugs used in combination with the anticoagulants, 2) the effect of substances found in the environment which could have an effect on their action, and 3) the effect of altered physiological states eq. liver damage. Emphasis will be placed upon the biliary excretion of the anticoagulants which provides a sensitive indicator of certain types of interactions. The anticoagulants are tightly bound by serum albumin as are quite a number of other drugs which could be involved in competitive displacement interactions which would accelerate the excretion of the anticoagulant. Such interactions will be studied in vitro and followed up by analysis in vivo. The basic studies will be carried out on the anaesthetized rats. Radioactive drug will be injected iv and samples of bile will be collected via a biliary cannula for radioactivity measurements. Acute drug interactions will be studied by the injection of a second drug at a later time. Chronic interactions will be studied by pre-treatment of the animal for induction studies or hepotoxicity studies.